Phenylalkylhydrazines and use as psychotherapeutics



3,090,903 Pl-IENYLALRYLHYDBES AND USE AS PSYCHGTiERAPEUTiQS John H. Biel, Milwaukee, Wis, assignor, by mesne assignments, to Lakeside Laborateries, Inc, Milwaukee,

Wis., a corporation of Delaware No Drawing. Filed Sept. 15, 1959, Ser. No. 840,016 15 Claims. (ill. 269-3405) This invention relates to hydrazine derivatives. More particularly, this invention is concerned with phenylalkylhydrazines and the use of these compounds as psychotherapeutic agents. The invention is also concerned with novel pharmaceutical compositions containing a phenylalkylhydrazine.

This application is a continuation-in-part of my copending applications Serial No. 605,724, filed August 23, 1956, now abandoned, Serial No. 716,876, filed February 24, 1958; Serial No. 780,193, filed December 15, 1958; and Serial No. 818,544, filed June 8, 1959.

It has been discovered, according to the present invention, that phenylalkylhydrazines have psychotherapeutic activity. The phenylalkylhydrazines which possess such activity, and are thus psychotherapeutic agents, have the formula:

methylenedioxy group, a halogen such as bromine or chlorine, and dihydroxy substituents, R is hydrogen, a lower alkyl group such as methyl, ethyl, isopropyl and the like, cycloalkyl groups such as the cyclohexyl and cyclopentyl groups, hydroxyalkyl groups such as the hy.

droxyethyl group, or an aralkyl group such as phenethyl, phenylpropyl and phenylisopropyl in which the alkyl moiety has at least two carbons in a straight or direct line between the nitrogen and the phenyl group, and R represents hydrogen, an alkyl group and particularly the lower alkyl groups such as methyl, ethyl, propyl, butyl, isopropyl, pentyl, hexyl and the like, a hydroxyalkyl group such as the ethylhydroxy group, an alkenyl group such as a lower alkenyl group and particularly the allyl group and the 1-(2-butenyl) group, an aryl group and particularly a monocyclic aryl group such as the phenyl' group and nuclear substituted phenyl groups such as the hydroxyphenyl, methoxyphenyl, chlorophenyl and acetoxyphenyl groups, an aralkyl group and particularly one in which the aryl moiety is monocyclic and the alkyl moiety is a lower alkyl group of at least two carbons in a direct or straight line between the phenyl and hydrazine moities such as phenethyl phenylpropyl, phenylisopropyl and pchlorophenylpropylgroups, a cycloalkyl group such as the cyclopentyl and cyclohexyl groups, an alkynyl group such as propynyl, butynyl and the like, the 2-thienylmethyl group and the pyridylmethyl group, and Y is a straight or branched alkylene group of at least two carbons in a direct or straight line between the phenyl and hydrazine groups and advisably of 12 or less carbons although it generally is of 5 or less carbons, such as the following:

(a) CH(CH )CH l-methylethylene (b) CH CH CH propylene rates Patent 0 2 (c) CH CH(CH 2- methylethylene (d) CH(CH )CH CH l-methylpropylene (e) CH CH(CH )CH Z-methylpropylene (f) CH CH CH(CH 3-methylpropylene (g) CH CH CH(CH )CH S-methylbutylene The compounds of Formula I are potent monoamine oxidase inhibitors and central nervous system stimulants useful for psychotherapeutic treatment of depressed mental states. Although I do not Wish to be restricted to a theory, it is considered that these phenylalkylhydrazines pass through the blood-brain barrier and, because of their monoamine oxidase inhibitory property, retard or prevent the metabolic destruction of neurohumoral agents such as serotonin and norepinephrine. Serotonin and norepinephrine are present in the brain and apparently serve as chemical transmitters in, or stimulants of, the central nervous system. A deficiency of available serotonin or norepinephrine' in the brain, such as can be caused by metabolism or degradation of these agents by monoamine oxidase, may result in parasympathetic predominance present in depressed mental states. By preventing or retarding destruction of serotonin and norepinephrine through the use of a phenylalkylhydrazine thelevels of these neurohumoral agents present in the body are maintained higher for longer periods of time so that sympathetic characteristics such as increased awareness and motility result.

Humans diagnosed as endogenous, tension, involutional, reactive, agitated and cyclic depressives as well as patients afflicted With depression secondary to schizophrenia or neurotic reactions have responded satisfactorily to the administration of phenylis-opropylhydrazine (N-(3-phenyl-2-propyl)hydrazine). Clinical improvement is characterized by elevation of mood, diminution of confusion, reduction in depressive attitudes and notable alertness.

Children with behavior patterns characterized by hyperactivity and irascibility have had excess motor activity quieted and were less asocial after being given phenylisopropylhydrazine.

In addition to phenylisopropylhydrazine, some other specific compounds which have been found to be exceptionally potent monoamine oxidase inhibitors are N-(3- p-methoxyphenyl 2 propyl)hydrazine, N-(3-o-methylphenyl-2-propyl)hydrazine, N (3 m chlorophenyl 2- propyl) hydrazine, N- [3 3',4-methylenedioxy) phenyl-2- propyH-hydrazine, N-(Z-phenyl-l-propyl)-hydrazine and N-(4-phenyl-2-butyl)-hydrazine.

The most potent monoamine oxidase inhibitors of Formula I are those in which Y has no more than three carbons in a straight line between the phenyl and hydrazine moieties and in which R is hydrogen, except 3-phenylpropylhydrazine which displays weak monoamine oxidase inhibition in animals. This does not mean that Y cannot have more than three compounds, for it can. The compound N-(4-phenyl3-butyl)hydrazine has four carbone in the chain but only three in a straight chain between the phenyl and hydrazine moities, but nevertheless is a very potent compound. Branching of the alkyl chain, and especially on the carbon atom bearing the hydrazine moiety will substantially increase monoamine oxidase inhibition. Although the compounds in which R is a substituent are active, those compounds in which R is hydrogen have higher activity.

Patented Sept. 19, 196i.

- 3 brain were prepared, some of which were used as untreated controls while the compounds to be tested were added to other portions of the homogenates. The metaboh'sm of serotonin (-hydroxytryptarnine) to S-hydroxyindole acetic acid in both the controls and the treated homogenates was measured over a 30 minute period. The reduction in metabolism of serotonin in the treated homogenates compared to the controls is reported as the percent inhibition.

The in vivo monoamine oxidase inhibitory activity was determined using the procedure reported by Chwsin et al. in the J. Pharm. and Exper. Therap. 119, 453 (1957). This test is based on the reversal effect which mono amine oxidase inhibitors have on reserpine treated ani- TABLE 1 In vitro inhibition concentration In vivo LD Ana- Oompound (=pheny1) of inhibitor activity mg./kg. leptic ipron- (S.C. mgJkg. iazid=1 mice) -M 10- M Iproniazid 0 1 1. OHz(|)H-NHNH2 H01 60 100 95 1.0

2. e-omom-Nnnm .HCl 30 4 102 3. -(|3HCH2NHNH2 .HaPCu 25 16 4. CH2CH2(])HNHNH: .HzSO; 80 100 20 5. CH2Cl HNHN'Ha .1101 10 100 8 118 10 CH: CHaO 6. 011210 CHaCl3H-NHNHa .1513 04 15 65 4 130 7. CHaO- CHz]CH-NHNH1 .HCl 5 50 2 100 l OHs CHsO OCH:

8. {O CHzICH-NHNH2 .1301 55 100 20 100 15 C 2 CH3 9. CHaffH-NHNH2 .HCl 45 100 20 114 12 CH3 CH3 10. CH2|CHNHNH2 .1131 O4 25 4 108 GHsCH 11. OHzCH-NHNHa .331? 04 49 20 84 3 12. -CH?HNHNHCH1 .HOI 3 126 10 13. -CH({3HNELNH(EHCH; .HCl 2 269 50 CH2 CH 14. CH2CI)H' NHNHCHCHQ 0 12 2 CH5 CH:

15. CHzCH2CH-NHNH3 37 91 Ha CHsO l Arousal from reserpine stupor.

inals. Normally an animal treated with reserpine shows a sedative effect. However, if pretreated with a'mono amine oxidase inhibitor, the animal will show a .pro-

nounced stimulatory effect when administeredreserpine.

This is called reserpine reversal. In carrying out the test, the compound to be studied is injected at a threshold concentration into a series of mice at various doses intraperitoneally and two hours later mg./kg; of. reserpine is injected intraperitone-ally. The lowest dose at which the animals show excitation is selected using iproniazid as l. The higher the number the more active is the compound.

These phenylalkylhydrazines also stimulate the heart muscle and are thus useful for the treatment of a person in a state of shock.

These compounds are hypotensor agents when administered to'humans and thus are useful in the treatment of hypertension. the blood pressure. The compound presently considered most useful as a hypotensor is phenylisopropylhydrazine administered as an acid addition salt.

Many of these compounds are many times more potent monoamine oxida'se inhibitors than iproniazid. Phenylisopropylhydrazine is particularly active and, in addition, is faster acting in humans than iproniazid.

The compounds of this invention are useful for potentiating other therapeutic agents, such as phenothiazine tranquilizers like prom-azine and and arouses an animal from reserpine stupor (induced by prior administration of reserpine) as well as stupor from administered barbiturates.

reserpine, a stimulating action results.

The compounds of Formula I which exert the described analeptic efiect, i.e., which arouse animals from reserpine induced stupor, are apparently only those in which Y is an isopropyl group, i.e., those in which the hydrazine moiety is bonded to the middle, or second carbon, in the chain, and the phenyl group is on a carbon at the end of the isopropyl chain.

When phenylisopropylhydrazine is administered to an animal followed by a barbiturate, the sedative action of the barbiturate is potentiated.

The compounds of this invention are themselves potentiated by chlorothiazide so that a greater hypotensor activity is obtained, such as when phenylisopropylhydrazine is administered.

These compounds, particularly phenylisopropylhydrazine, are also useful in treating angina pectoris.

Phenylisopropylhydrazine is also useful as arthritic agent.

Several methods of preparing the compounds of Formula I may be employed. In one method a suitable phenylalkylhalide is reacted with hydrazine or a monosubstituted hydrazine to form the corresponding phenylalkylhydrazine. This process may be represented as follows:

an anti- Wherein X is a reactive halogen such as chlorine, bromine or iodine, and R, R, and Y have the significance previously assigned.

In addition to hydrazine hydrate, monosubstituted hydrazines such as methylhydrazine, ethylhydrazine, phenethylhydrazine, phenylhydrazine, propargylhydrazine, allylhydrazine, hydroxyethylhydrazine, p-chlorophenylpropylhydrazine, cyclohexylhydrazine, 2-pyridylmethylhydrazine and the like may be used.

Phenylalkylhalides in which the alkyl moiety is ethyl or larger may be used in the process including phenylethylhalide, p-chlorophenylisopropylchloride, 4-(p-methoxyphenyl)-2-methyl butylchloride, 3,4-methylenedioxy- In the dog, however, they raise.

ohloropromazine. However, phenylisopropylhydrazine is an analeptic agent Nevertheless, if phen-- ylisopropylhydrazine is administered first, followed by phenylethylchloride, phenyloctylchloride, 'pphenoxy phenylpropylbromide, m-methylphenylhexylchloride and the like.

The reaction is eifected by adding the phenylalkylhalide very slowly to a solution of a large excess (200%) of the hydrazine reactant in a solvent such as methanol, ethanol, butanol or dioxane. Increased temperatures such as up to reflux temperature are generally employed to increase the reaction rate. By distilling ofi the solvent, extracting the residue with a solvent such as ether and then iractionally distilling the extract, the desired reaction product may be recovered.

Representative of the products which are produced in this way are beta-phenylethylhydrazine, N-(3-phenyl-2- propyl) hydrazine, N-phenylhexyl-N-methyl hydrazine, N- (p-chlorophenylpropyl) -N-phenylisopropyl hydrazine, N- 3 ,4-methylenedioxyphenylethyl) -N-cyolohexyl hydrazine, N-phenyl ethyl-N-phenyl hydrazine, p-hydroxyphenylbutylhydrazine, N-phenylethyl-N-hydroxyethyl hydrazine and N-phenylpropyl-N-Z-pyridylmethyl hydrazine.

The phenylalkylhydrazines may also be produced by the process which comprises reacting hydrazine or an N- substituted hydrazine with a phenylalkylaldehyde or a phenylalkyl-alkylketone to form an intermediate hydrazone which is then reduced to the desired hydrazine. This process may be represented as follows:

wherein R and R have the significance previously assigned, Z is a lower alkylene group, R is hydrogen or a lower alkyl group, and

-ZOH

is equivalent to the significance assigned to Y previously.

Some of the phenylalkyl aldehydes and phenylalkyl alkyl ketones which may be used in this process are phenylethylaldehyde, phenylacetone, 2-phenylpropionaldehyde, p-chlorophenylbutyraldehyde, 3,4-methylenedioxyphenylvaleraldehyde, phenylacetal, p-hydroxyphenylacetaldehyde, phenylethyl methyl ketone, phenylbutyl ethyl ketone, Z-phenylpropyl propyl ketone, phenylethyl' ethyl ketone, 3,4-methylenedioxyphenylacetone, p-hydroxybenzyl methyl ketone, o-methylbenzyl methyl ketone, mchlorobenzyl methyl ketone and m-propoxybenzyl ethyl ketone and the like.

In addition to hydrazine, monosubstituted hydrazines tacting the reactants in the presence of water or a lower' alcohol. The reaction proceeds at room temperature although slightly elevated temperatures may be employed to increase the rate of reaction. Recovery of the intermediate phenylalkylidenyl hydrazine, or hydrazone, is conveniently effected by conventional methods. Thus, the product, generally an oil as the free base, may be salted out with an alkali metal hydroxide and extracted with a water immiscible organic solvent such as ether. The product is readily isolated by distillation under reduced pressure.

The intermediate hydrazone may be reduced to the corresponding hydrazine by chemical or catalytic reduction. Lithium aluminum hydride is the preferred chemical reducing agent. With lithium aluminum hydride, the reduction may be conveniently effected by intimately combining the reactants in an inert organic solvent such as anhydrous ether, dioxane, or tetrahydrofuran. Elevated temperatures such as the reflux temperature enhance the reaction. At reflux temperature, from 1 to 8 hours is usually suflicient to substantially complete the reaction. After the reaction is terminated, water may be added to the mixture to decompose excess'lithium aluminum hydride. T recover the product, the organic phase is separated and the aqueous residue then may be combined, dried, and the product distilled.

Catalytic reduction may also be used satisfactorily using catalysts such as rhodium, platinum oxide, palladium and the like in solvents such as tetrahydrofuran, water, ethyl acetate and dioxan. Raney nickel is not a particularly suitable catalyst since undue cleavage occurs. Hydrogen pressures of about 50 to 3000 psi. may be used. The temperature of reduction may be room temperature or increased temperatures such as up to 80 C.

For reducing the monosubstituted hydrazones, i.e., the phenylalkylhydrazones, it is advisable to use platinum or platinum oxide and conduct the reduction in a lower alcoholic solution containing a molar amount of acetic acid equal to the hydrazone to be reduced.

Some of the hydrazines produced in this way are phenylethylhydrazine, N-(3-phenyl-2-propyl) hydrazine, N- phenylpropyl-N'-ethyl hydrazine, N-pl1enylbutyl-N-cyclohexylhydrazine, N-phenylhexyl-N'-phenylpropyl hydrazine, N-3,4-methylenedioxyphenyl-ethyl- '-propyl hydrazine, N-phenylethyl-N'-phenyl hydrazine, N-(3-phenyl-2- propyl)-N'-methyl hydrazine, sym. bis-N,N-(phenylisopropyl)hydrazine, N [3 (p chlorophenyl)-2propyl]-N'- methyl hydrazine, N-[4-(o-hydroxyphenyl)-2-butyl]-N'- ethyl hydrazine, N (5 phenyl 3 amyl)-N-pbenylethyl hydrazine, N-(4-phenyl-2-butyl)-N'-ethyl hydrazine, N-(3- phenyl-2-propyl)-Nallyl hydrazine and the like.

Hydrazines of Formula I in which R is a lower alkyl or aralkyl group and R is hydrogen may be conveniently produced be reacting an N-lower alkyl or aralkyl-N- (phenylalkyl)amine with nitrous acid to form the corresponding N-nitroso-N-lower alkyl or aralkyl-N-( phenylalkyDamine and reducing such compound to the corresponding N-nitroso-N-lower alkyl or aralkyl-N-(phenas follows:

R Br

mediate may be recovered. It may be purifiedb y fractional distillation.

Reduction of the nitroso compound to the corresponding hydrazine may be conveniently achieved by chemical or catalytic methods such as described hereinabove. Representative compounds formed in this manner are N-amino N-methyl phenylisopropylamine, N-amino-N- ethyl pmethoxyphenylhexylamine, N-amino-N-phenethyl p hydroxyphenylethylamine, N amino N propyl- 3,4 methylenedioxyphenylisopropylamine, N amino- N-methyl-N-(Q-phenylbutyl) amine and N-amino-N-ethyl- N- (3 -phenylamyl) amine.

The described hydrazines are advisably employed in the described uses in the form of nontoxic acid addition salts such as the hydrochloride, hydrobromide, fumarate, phosphate and sulfate.

The phenylalkylhydrazines may be administeredto'animals and humans as pure compounds. It is advisable, however, to first combine one or more of the novel compounds with a suitable pharmaceutical carrier to attain a more satisfactory size to dosage relationship.

Pharmaceutical carriers which are liquid or solid may be used. The preferred liquid carrier is water. :Flavoring materials may be included inthe solutions as desired.

Solid pharmaceutical carriers such as starch, sugar, talc, manitol and the like may be used to form powders. Mannitol is the preferred solid carrier. The powders may be used as such for direct administration to a patient or, instead, the powders may be added to suitable foods and liquids, including Water, to facilitate administration.

The powders also may be used to make tablets, or to fill gelatin capsules. Suitable lubricants like magnesium stearate, binders such as gelatin, and disintegrating agents.

Mg. (1) N-(3-phenyla2-propyl)hydrazine HCl 12.5 (2) Mannitol (.3) Stearic acid 3 A granulation is made from the mannitol. The other ingredients are added to the dry granulation and then the tablets are punched.

Another tablet may have the composition:

Mg. (1) 2-phenylpropylhydrazine HCl 15 (2) Mannitol 100 (3) Stearic acid 3 Powders 1, 2 and 3 are slugged, then granulated, mixed with 4 and 5, and tableted.

Capsules may be prepared by filling No. 3 hard gelatin capsules with the following ingredients, thoroughly mixed:

( 1 N-methyl-N'-(3-phenyl-2propyl)hydrazine Mg.

HCl 5 (2) Lactose U.S.P 200 (3) Starch U.S.P l6 (4) Talc U.S.P 8

The oral route is preferred for administering the active phenylalkylhydrazines.

Dosages of from about 1 mg. to 50 mg. may be ad ministered to obtain the stated activities. However, the recommended dosages are from '3 to -12 mg. daily. Larger dosages may be administered on an interrupted schedule but generally not more than 50 mg, and preferably not more than 25 mg, is administered daily.

According to a further embodiment of this invention, one or more of the phenylalkylhydrazines is administered s multaneously with, or concomitantly to, the administraton of either tryptophan and/or phenylalanine to an amn al or human. Tryptophan passes the blood-brain barrrer'and is converted in the brain to serotonin. Serotomn is not administered directly since it cannot pass the blood-brain barrier. Similarly, phenylalanine passes the blood-brain barrier and is converted in the brain to norepinephrine. Norepinephrine itself will not pass the blood-brain barrier so it is not given directly.

In place of tryptophan and phenylalanine one may use S-hydroxytryptophan and 3,4-dihydroxy phenylalanine since the body first converts the amino acids to these respective hydroxyl derivatives.

By the administration of an active phenylalkylhydrazine simultaneously with, or concomitantly to, either tryptophan or phenylalanine, the monoamine oxidase inhibitory property of the hydrazine retards or prevents the degradation of serotonin and/or norepinephrine which are produced in the brain from the said amino acids. The serotonin and norepinephrine levels are thus not only raised but are maintained at the increased level by the described treatment.

Any suitable amounts of tryptophan (or S-hydroxytryptophan) and/ or phenylalanine (or 3,4-dihydroxy phenylalanine) may be administered since these materials are nontoxic. One or both of these materials is advisably combined with one or more of the active phenylalkylhydrazines into suitable pharmaceutical formulations.

According to another embodiment of the invention, reserpine can be administered simultaneously with, concomitantly to, or subsequent to, the administration of the phenyalkylhydrazine to obtain an added stimulatory effect as is evidenced by the reserpine reversal of the in vivo test referred to herein previously.

The following examples illustrate methods of making the compounds.

EXAMPLE 1 Beta-phenethylhydrazine To a refluxing solution containing 147.5 g. of 85% hydrazine hydrate in 500 cc. of ethanol was added, during a period of 5 hours, 92.5 g. of phenethylbromide (0.50 mole) in 150 cc. of ethanol. Stirring and refluxing were continued for two hours. The ethanol was removed by distillation and the residue extracted repeatedly with ether. The ether was dried with potassium carbonate and the product collected by distillation, B.P. 74 C./0.1 mm., yield 52.3 g. (77%); N 1.5494.

Analysis.Calcd. for C H N N, 20.57. Found: N, 20.85.

EXAMPLE 2 Phenethyl hydrazine hydrochloride The salt was prepared in ethanol by the addition of ethereal hydrochloric acid to the base, M.P. 167 C.

Analysis.-Calcd. for C l-I ClN Cl, 20.53. Found: Cl, 20.71.

EXAMPLE 3 Z-phenylpropylidanyl hydrazine -05 om oH=N-Nrn 100.5 g. (0.75 mole) of Z-phenylpropionaldehyde was added during a period of 2 hours to 132.5 g. of 85% hydrazine hydrate at room temperature in 500 cc. methanol. After standing at room temperature for two hours, the methanol was removed and water was added to the residue. The aqueous mixture was saturated with potassium hydroxide and extracted with ether. The product was collected by distillation at 83 C./ 0.08 mm., yield (90%); N 1.5610.

Analysis.-Calcd. for C H N N, 9.45. Found: N, 8.88.

10 EXAMPLE 4 1 -hydrazino-2-phenyl propane EXAMPLE 5 N-(3-phenyl-2-propyl) hydrazine To 106 g. of aqueous N H --H 0 (1.8 mole) in 500 cc. of methanol was added 120.8 g. (0.90 mole) of phenylacetone with stirring and cooling, keeping the temperature between 1520 C. The mixture was stirred for four hours at room temperature. The methanol was removed by distillation and the residue dissolved in 400 cc. of ether. The ether solution was dried with potassium carbonate and the ether removed by distillation. One hundred gms. of the residue was dissolved in 300 cc. of ethanol and hydrogenated in the presence of 40 g. of acetic acid and 1.0 g. of platinum oxide catalyst at room temperature and a pressure of 60 lbs. H The solution was clarified by filtration, the solvent distilled, the residue dissolved in water, the aqueous solution saturated with solid potassium hydroxide and the alkaline mixture extracted repeatedly with ether. The product was collected by distillation at 70 C. (0.02 mm.); N 1.5373; yield 53 g. (46%).

Analysis.--Calcd. for C H N N, 18.66. Found: N, 18.54.

EXAMPLE 6 N-(3-phenyl-2-propyl)-hydrazine hydrochloride The base of Example 5 was neutralized with ethereal hydrochloric acid in 1:1 ether-isopropyl alcohol solution and the precipitate collected by filtration; M.P. 116 C.

Analysis.Calcd. for C H ClN Cl, 19.03. Found: Cl, 19.00.

EXAMPLE 7 N-methyl-N'-(3-phenyl-2-propylidenyl) hydrazine To 48 g. of mono-methylhydrazine sulfate in 325 cc. of Water was added 40.1 g. or": 28% ammonium hydroxide and then 40.2 g. of methyl benzyiketone in 300 cc. of methanol keeping the temperature at 3035 C. The pH of the reaction mixture was adjusted to 6 with acetic acid. Methanol was then removed by distillation, the residue dissolved in water, the aqueous solution saturated with solid potassium hydroxide, the alkaline mixture ex- 11 tracted with ether and the extractsdried with potassium carbonate. The product was collected at 83 C. (1.0 mm.); yield 21 g. (43%); N 1.5442.

Analysis.-Calcd. for C H N N, 17.26. Found: N, 16.98.

EXAMPLE 8 N-methyl-N-(3-phenyl-2-pr0pyl) -hydrazine and its hydrochloride A mixture containing 20.5 g. of the propylidene derivative of Example 7, 7.5 g. of glacial acetic acid, 75 cc. of ethanol and 0.3 g. of platinum oxide catalyst was subjected to hydrogenation at 50 lbs. psi. and room temperature. The catalyst was removed by filtration, the solvent distilled off and the residue dissolved in water. A saturated aqueous potassium hydroxide solution was added to the residue and the mixture extracted with ether. The ether extracts were dried with potassium carbonate and the product collected by distillation; B.P. 78 C. (1 mm); yield 14.9 g. (71%); N 1.5205.

Analysis.-Calcd. for C1QH16N2: N, 17.06. N, 16.86.

To 18 g. of the base dissolved in an ether isopropyl alcohol solution (8:3) was added ethereal hydrochloric acid. The precipitate was collected by filtration, yield 1.6 g., M.P. 155417 c.

Analysis.-Calcd. for C H ClN Cl, 17.66. Found: Cl, 17.99.

Found:

EXAMPLE 9 N-nitroso-N-(3-phenyl-2-propyl) -methylamine To 92.8 g. (0.44 mole) of N-methyl phenylisopropylamine hydrochloride in 100 cc. of water and 26 cc. (0.54 mole) of cone. hydrochloric acid cooled to 5-10 C. was added slowly a solution of 85 g. (1.2 moles) of sodium nitrite in 150 cc. of water, so as to maintain the reaction at 5-10 C. After extraction of the reaction mixture with ether and removal of the solvent the product was fractionated, B.P. 115-116 C. (0.8 mm), yield 77.3 g. (87%).

EXAMPLE N-amino-N-methyl phenylisopropylamine Found: N,

EXAMPLE 11 3,4-methylenedioxyphenylisopropylhydrazine To 29.5 g. (0.50 mole) of hydrazine hydrate in 150 cc. of methanol was added, during one hour at 510 C., 44.5 g. (0.25 mole) of 3,4-methylenedioxyphenylacetone. The solution was stirred for 2.5 hours. The methanol was removed by distillation. To the residue was added 150 cc. of absolute ethyl alcohol and 15 g. (0.25 mole) of glacial acetic acid and 500 mg. of platinum oxide and the mixture subjected to hydrogenation at 60 lbs. of hydrogen and room temperature. The catalyst was removed by filtration and the product recovered by fractional distillation, yield 31.9 g. (66%); B.P. 130 C./0.6 mm.

Analysis.Calcd. for G T-1 N 0 N, 7.22. Found: N, 6.84.

EXAMPLE 12 Sym-bis-N,N'-(phenylisopropyl) -hydrazine To 106 g. (1.8 moles) of 85% hydrazine hydrate in 500 cc. of methanol was added 120.6 g. of phenylacetone with stirring. The solution was stirred for 1 hour at room temperature and then refluxed for 15 minutes. The methanol was removed by distillation and the residue extracted with ether. The ether was removed by distillation, the residue dissolved in a mixture of 150 cc. of ethanol and 54 g. of glacial acetic acid and subjected to hydrogenation in the presence of 600 mg. Pt0 at 60 lbs. of hydrogen and at room temperature. After removal of the catalyst by filtration the product was collected at 140 C. (0.02 mm.); yield 43.0 g. (35.6%).

Analysis.--Calcd. for C H N Titratable N, 5.22. Found: Titratable N, 5.26.

EXAMPLE 13 N-(1 -phenyl-2-propyl) -N'-isopropylidenyl hydrazine Found:

EXAMPLE 14 N (1 -phenyl-2-propyl) -N'-is0pr0pyl hydrazine To a solution of 22.2 g. of N-(phenylisopropyl)-N'- isopropylidenyl hydrazine (0.117 mole) in 70 cc. of ethanol was added 7.9 g. of acetic acid (0.117 mole). The solution was reduced in the Parr apparatus in the presence of 0.18 g. of platinum oxide catalyst; in about hour the theoretical amount of hydrogen had been absorbed and further uptake of hydrogen ceased. The catalyst was removed by filtration and the filtrate was concentrated under vacuum. The syrupy residue was dissolved in cc. of water, and, with cooling, the solution was saturated with potassium hydroxide. The alkaline mixture was extracted 3 times with 55 cc. portions of ether. The ethereal extracts Were dried over potassium carbonate, and the ether distilled off through a 14" column. The ethereal residue was subjected to vacuum distillation through a 5" column. The liquid, B.P. -122 C./13 mm., was collected as product; yield 65 g. (76%), N 1.5022.

Analysis.-Calcd. for C H N N, 14.57. N, 13.98.

The hydrochloride salt melted at 149-150 C.

Analysis.--Calcd. for C H ClN Cl, 15.54. Found: Cl, 15.53.

Found 13 EXAMPLE 1s Benzylacetone hydrazone A solution of 49.3 g. of benzylacetone (0.33 mole) in 100 ml. of methanol was added in 3 hours with stirring to a refluxing solution of 59 g. of hydrazine hydrate (85 in 175 ml. of methanol. The solution was stirred for 2 more hours and the methanol was then removed by distillation. To the solution was added 350 ml. of ether. The ethereal solution was Washed with 50 ml. of water. The ether solution was dried over anhydrous potassium carbonate. The solvent was removed by distillation, and fractionated through a 6" Vigreux column; yield 46.5 g. (86%), HP. 96 C./0.07 mm, N 1.5521.

Analysis.-Calcd. for C H N N, 17.26. N, 16.86.

From the high boiling residue, benzylacetone azine was obtained, B.P. 160 C./0.015 mm., N 1.5616.

Analysis.-Calcd. for C H N N, 4.79. Found: N, 4.74.

F und EXAMPLE 16 1-phenyl-3-hydrazino butane In 250 ml. of ethanol was dissolved 52.2 g. of benzylacetone hydrazone (0.322 mole). The hydrazone was neutralized with 19.3 g. of acetic acid (0.322 mole), transferred to a Parr bottle and 500 mg. of platinum oxide catalyst was added. The mixture was reduced at room temperature and 60 psi. of hydrogen. The catalyst was removed by filtration, and the alcohol by distillation. Water was added to the residue which was made alkaline with solid potassium hydroxide. The alkaline mixture was extracted with ether and dried over anhydrous potassium carbonate. The solvent was removed by distillation and fractionated through a 2" Vigreux column; yield 36.4 g (69%), BR 82 C./0.025 mm., N 1.5333.

Analysis.Calcd. for C H N z N, 1706. Found: N, 1636.

During distillation of this base a high boiling fraction was obtained consisting of N,N'-bis-[(4-phenyl)-2-butyl] hydrazine, B.P. 150 C./0.02 mm., N 1.5455.

Analysis.Calcd. for C H N N, 9.46. Found: N, 9.26.

EXAMPLE 17 1-phenyl-3-hydrazin0 butane sulfate In 500 ml. of isopropanol was dissolved 30.9 g. of base from Example 16. A solution of 20 g. of sulfuric acid was added in 80 ml. of water. The solvents were removed by distillation in vacuo, and a syrup remained. The mass was dissolved in 400 ml. of hot isopropanol, cooled, 1000 ml. of dry ether added and crystallization induced by seeding. The precipitate was removed by filtration and dried; yield 38.5 g., M.P. 92 C. The salt could be recrystallized from fold amount of acetonitrile or a fold amount of ethyl acetate; M.P. 96 C.

Analysis.Calcd. for C H N O S: N, 10.86. Found: N, 11.01. Sulfuric'acid: 37.37. Found: 37.82.

EXAMPLE 18 1-(3'-chl0r0phenyl) -2-hydrazinopr0pane A solution of 42.5 g. of 3-chlorophenyl acetone (0.252 mole) in 400 ml. of methanol was added in 6 hours to a stirred refluxing solution of 45.5 g. of hydrazine hydrate (85%) in 600 ml. of methanol. The solution was stirred and refluxed for 2 more hours. The methanol was removed by distillation, the remaining portion was extracted with ether, and washed with 50 ml. of water. The ethereal extracts were dried over anhydrous potassium carbonate. The solvent was removed by distillation; residue, 45.4 g. The residue was dissolved in 225 ml. of ethanol, transferred to a Parr bottle, 14.8 g. of acetic acid added and was followed by 750 mg. of platinum oxide catalyst. The mixture was reduced at 60 p.s.i. of hydrogen. The catalyst was removed by filtration, and the alcohol by distillation. Water was added to the residue which was then made strongly alkaline and extracted with ether. The ethereal extracts were dried over anhydrous potassium carbonate. The solvent was removed by distillation and the remaining portion fractionated through a 4" Vigreux column; yield 20.0 g. (43%), 13.1. 860 C./ 0.1 mm., N 1.5522.

Analysis.-Calcd. for C H CIN N, 15.09; Cl, 19.09. Found: N, 12.66; Cl, 19.23.

The compound lost nitrogen on standing at room temperature.

EXAMPLE 19 1-(3'-chlor0phnyl) -2-hydrazinopr0pane phosphate In 250 ml. of ethanol was dissolved 21 g. of the base from Example 18. The mixture was heated to boiling and added to a solution of 13.2 g. of phosphoric acid in ml. of ethanol. The mixture was cooled, filtered, rinsed with ethanol, and dried; yield 30 g., starts to shrink at ca. 125 C., melts and decomposes ca. 265 C.

Analysis.--Calcd. for C H ClN O P: N, 9.88; phosphoric acid, 34.55. Found: N, 9.92; phosphoric acid, 34.62.

EXAMPLE 20 1-(4-meth0xyphenyl) -2-pr0pylidenyl hydrazine To a solution of 51 g. of hydrazine hydrate (85%) (0.87 mole) in 125 ml. of methanol was added with stirring at 10-20" C. in 2 hours a solution of 71.5 g. of 4- methoxyphenylacetone (0.435 mole) in 100 ml. of methanol. The solution was stirred for 3 hours at room temperature. The methanol was removed by distillation, and 300 ml. of ether added. The aqueous hydrazine layer was separated and extracted again with ether. The combined ethereal extracts were dried over potassium carbonate. The solvent was removed by distillation and the remaining portion fractionated through a 4" Vigreux column; yield 44.6 g. (57.6%), B.P. 124 C./0.015 mm., N 1.5615.

Analysis.--Calcd. for C H ON N, 15.72. Found: N, 15.22.

EXAMPLE 21 1-(4'-meth0xyphenyl) -2-pr0pyl hydrazine In 200 ml. of ethanol was dissolved 39.2 g. of 2(4 methoxy)-phenylisopropylidenyl hydrazine (0.22 mole). The base was neutralized with 13.2 g. of acetic acid (0.22 mole), transferred to a Parr bottle and 400 mg. of platinum oxide catalyst was added. Reduction proceeded rapidly at room temperature and 60 psi. of hydrogen pressure. The catalyst was removed by filtration and the alcohol by distillation. Water was added to the residue and made strongly alkaline with potassium hydroxide. The oil was extracted With ether and the extracts dried over anhydrous potassium carbonate. The solvent was removed by distillation, and the residue fractionated through a 4" Vigreux column; yield 23.4 g. (59.1%), B.P. C./0.'03 mm., N 1.5403.

Analysis.-Calcd. for C H CN N, 15.56. Found: N, 15.36.

The hydrochloride salt was made by dissolving 20.2 g. of the base in a mixture of 200 m1. of dry ether and 200 m1. of isopropanol. Ethereal HCl was added until pH 3. On cooling, the hydrochloride crystallized out; yield 18.6 g., M.P. l30131 C. The salt can be recrystallized from a 10 fold amount of acetonitrile.

Analysis.Calcd. for C1QH17ONZCII N, 6.46; C1, 16.36. Found: N, 6.57; Cl, 16.56.

15 EXAMPLE 22 Z-methylphenyl acetone hydrazone A solution of 49.3 g. of Z-methylphenyl acetone (0.33 mole) in 200 ml. of methanol was added with stirring at ca. 20 C. in 3 hours to a solution of 59 g. of hydrazine hydrate (85%) (1.0 mole) in 300 ml. of methanol. The solution was stirred for 2 more hours. The methanol was removed by distillation, and the residue extracted vw'th ether. The ethereal extracts were dried over anhydrous potassium carbonate and the solvent was removed by distillation. The remaining portion was fractionated through a 10 Vigreux column; yield 42.9 g. (79.3%), B.P. 93 C./0.04 mm, N 1.5621.

Analysia-Calcd. for C H N N, 8.69. Found:

EXAMPLE 23 1-(2-methylphenyl) -2-hydrazino propane In 250 ml. of ethanol was dissolved 40.8 g. of Z-methylphenyl acetone hydrazone (0.252 mole). The hydrazone was neutralized with 15.1 g. of acetic acid (0.252 mole), transferred to a Pen bottle and 550- mg. of platinum oxide catalyst added. Reduction proceeded rapidly at room temperature and 60 p.s.i. of hydrogen pressure. The catalyst was removed by filtration, and the alcohol by distillation. Water was'added to the residue and made strongly alkaline with potassium hydroxide. The residue was extracted with ether, and dried over anhydrous potassium carbonate. The solvent was removed by distillation and the residue fractionated through'a 12 Vigreux column; yield 15.9 g. (38.5%), B.P. 814.5 C./0.04 mm., N 1.5399.

Analysis.Calcd. for C H N t N, 17.06. Found: N, 16.67.

The hydrochloride salt was made by dissolving 1.64 g. of the base (0.01 mole) in a mixture of 10 ml. of isopropanol and 20 ml. of dry ether. Added ethereal HCl until pH 5. On cooling the hydrochloride crystallized; yield 1.8 g., MP. 122 C. The salt could be, recrystallized from a 20 fold amount of hot acetonitrile. M.P. 127 C.

Analysis.-Calcd. for C10H17N2C1: N, 13.96; Cl, 17.66. Found: N, 13.82; Cl, 17.97.

The phosphate salt was prepared from 0.82 g. of the base (0.005 mole); yield 1.3 g., shrinking at ca. 150 C., no clear melt.

Analysis.Calcd. for C H O N P: N, 10.68; phosphoric acid, 37.38. Found: N, 10.49; phosphoric acid, 37.73.

EXAMPLE 24 3',4' -dimethoxyphenyl acetone hydrazone 1- (3,4-dimethoxyphenyl) -2-propyl hydrazine The hydrazone of Example 24 was reduced with platinum oxide and glacial acetic acid in ethanol as in Example 23, yield 45%, B.P.. 132 C. (0.04 mm.). Nitrogen evolved on distillation.

AnfllYSiS.-Q31Cd. fOl' CHI-118N202: N, Found:

The phosphate salt melted at ca. ISO-160 C. dec. Analysis.-Calcd. for C I-[ 19 1 N, 9.08; phosphoric acid, 31.80. Found: N,' 9.23;. phosphoric acid, 7

16 EXAMPLE 25 3',4', -trimethoxyphenyl acetone hydrazone The hydrazone was prepared as in Example 22 from the appropriate reactants, B.P. 156 C. (0.05 mm.).

Analysis.Calcd. for C H N O C, 72.92; H, 8.18; N, 11.76. Found: C, 72.98; H, 8.22; N, 11.44.

EXAMPLE 27 1-(3',4,5-trimethoxyphenyl) -2-n'ropyl hydrazine The hydrazone of Example 26 was reduced with platinum oxide in ethanolic acetic acid as in Example 23; yield 54%; B.P. 142 C. (0.03 mm), N 1.5424.

Analysis.-Calcd. for C I-1 N 0 N, 11.60. Found: N, 11.91.

The hydrochloride salt melted at 150 C.

Analysis.-Calcd. for C H ClN O Cl. 12.81; N, 10.12. Found: Cl, 12.87; N, 10.35.

EXAMPLE 28 4-methoxyphenylbutan0ne hydrazone The hydrazone was prepared in 49% yield from the ketone and hydrazine hydrate in methanol; B.P. 134 C. (0.10 mm.); N 1.5510.

Analysis.-Calcd. for C H N O: N, 14.56. Found: N, 13.32.

EXAMPLE 29 I (4 -methoxyphenyl -3-bzltyl hydrazine EXAMPLE 30 4-isopropylphenyl acetone hydrazone This compound was prepared from isopropylphenyl acetone and hydrazine hydrate as in the previousexamples, B.P. 117 C. (0.12 mm.).

Analysis.-Calcd. for C H N N, 14.72. N, 14.70.

Found EXAMPLE 31 1-(4Fisopropylphenyl) -2-hydrazin0pr0pane The hydrazone of Example 30 was reduced with hydrogen using platinum oxide and glacial acetic acid in ethanol, B.P. C. (0.1 mm.).

Analysis.-Calcd. for C H N N, 14.56. Found: N, 14.32.

The phosphate salt melted at ca. 158 C.

Analysis.-Calcd. for C H N .H PO N, 9.65; H PO 32.93. Found: N, 9.88; H P0 33.10.

EXAMPLE 32 N-2-(3-phenyl)-butyZidenyl-N-carbethoxy hydrazine A solution of 41.6 g. (0.4 mole) of carbethoxyhydrazine in 50 cc. of ethanol was added to a refluxing solution of 59.2 g. (0.4 mole) of 2-phenyl butanone-3 in 120 cc. of ethanol. After a 5 hour reflux period the alcohol was distilled off and the viscous residue was poured into 700 cc. of heptane. On refrigeration a voluminous white solid formed which was filtered, washed with heptane and dried. Yield 71.3 g. (76%), M.P. 86 C.

There was dissolved 56.2 g. (0.24 mole) of N-2-(3- phenyl)-butylidene-N'-carbethoxy hydrazine in 200 cc. of

.methanol, 14.4 g. of acetic acid was added, and the hydrazone was reduced in the presence of 800 mg. of Pt0:

s',ooo',oos

catalyst at room tempe'r'ature'and 60 lbs. of hydrogen.pres-.. sure. The catalyst was removed by filtration. and the methanol was removed by distillation. .The residue .was taken up in aqueous. alkali, extracted with ether, dried and the ether was removed by distillation. The residue was stirred and refluxed for 4 hours with a solution of 40 g. of sodium hydroxide in 560 cc. of aqueous methanOl 1:1. After cooling, the sodium carbonate was filtered off and most of the methanol was distilled otf. After adding conc. aqueous alkali the solution was extracted with ether and dried over K CO anhyd. After filtration, the ether was removed by distillation and the residue was fractionated through a 4" column. There was obtained 19.8 g. (51%), boiling at 79 C./0.3 mm., N 1.5341. g r I? Analysis.-Calcd. for C H N z N, 17.06. Found: N, 15.82.

Hydrochloride salt.-18.6 g. of the base was dissolved in a mixture of 250 cc. of dry ether and 150 cc. of ethanol and ethereal HCl was added until the pH was 1. After refrigeration and addition of 800 cc. Ofdry ether, there was obtained 11.5 g. of white salt, M.P. 124-126 C.

Analysis.-Calcd. for CmHmClNgl N, 13.96; Cl, 17.66. Found: N, 14.02; Cl, 17.85.

EXAMPLE 34 N-(o-chlorophenylisopropylidenyl) -N'--'carbethoxyhydrazine A solution of. 20.8 g. (0.2 mole). of carbetho'xyhydrazine in 25 cc. of ethanol was .added at reflux temperature in 10 min. to a. solution of 34.2 g. (0.2 mole) of ortho chlorophenylacetone in 60 cc. of-ethanol. After refluxing for 5 hours the alcohol was distilled 0115. The remaining syrup was stirred with 100 cc. of heptane which induced crystallization. The .solid was filtered, washed with heptane and dried. Yield 48.3 g. (95%), M.P. 102 C.

Analysis.-Calcd. 01 CmHmClNgOgZ Cl, 13.92. Found: Cl, 13.86.

EXAMPLE 35 l-(o-chlorophenyl)-2-hydrazinoplropane and hydrochloride salt 46.4 g. (0.18 mole) of N(o-chlorophenyl)-isopropylidene-N'-carbethoxy hydrazine was dissolved in 200 cc. of methanol and 10.8 g. (0.18 mole) of acetic acid added. The mixture was then reduced in the presence of 800 mg. of platinum oxide catalyst at room temperature and 60 lb. of hydrogen pressure. The catalyst was removed by filtration and the methanol was removed by distillation. The residue was taken up in water, made strongly alkaline by addition of potassium hydroxide and the base was extracted with ether and dried over sodium sulfate. The ether was then removed by distillation. The 44.5 g. of viscous residue was refluxed for 4 hours with a solution of 39 g. of KOH in 400 cc. of aqueous methanol 1:1. The methanol was distilled oil and the resulting oil was extracted with ether, dried over potassium carbonate, filtered and fractionated through a short column. There was collected 19.8 g. (85.5%) at 88 C./0.1 mm., N 1.5539.

Analysis.-Calcd. for C H ClN N, 15.17 Found: N, 14.63.

Hydrochloride salt.--The hydrochloride was prepared by adding ethereal hydrochloric acid to a solution of the base in alcohol-ether. The salt was recrystallized from a 25 fold volume of acetonitrile, M.P. 120-121" C.

Analysis.-Calcd. for C H CI N N, 12.67; ionic Cl, 16.03; total Cl, 32.07. Found: N, 12.73; ionic Cl, 16.34; total Cl, 31.95.

EXAMPLE 36 N-phenylisopropylidenyl-N'-benzyl hydrazine Into a 1000 cc. S-neck round bottom flask equipped with stirrer, reflux condenser and addition tunnel was placed a solution of 61.0 g. of benzylhydrazine (0.5 mole) t" in 250 cc. of isopropyl alcohol. At reflux temperature a solution of 67.0 g. of phenylacetone (0.5 mole) in250..

' EXAMPLE 37 N-(1-methyl-2-phenethyl)-N '-benzyl hydrazine To a solution of 103.4 g. of N-phenylisopropylidenyl- N'-benzyl hydrazine (0.43 mole) and 26.0 g. of acetic acid (0.43 mole) in suflicient ethanol to prepare 350 cc. of solution was added 1.0 g. PtO The solution was hydrogenated at 1400 p.s.i.; in 2 /2 hours the theoretical pressure drop occurred. The catalyst was filtered OE and the ethanol removed under -vacuum. The residue was suspended in 200 cc. of water and saturated with KOH. The alkaline mixture was extracted 3 times with 75 cc.

portions of ethyl ether, and after drying the ethereal.

solution over K CO the ether was distilled off through a 14" column. The residue was distilled through a 3",' Vigreux column; B.P. 129-134 C./0.1-0.2 mm., N53

1.5609; yield 75.7 g. (73.4%).

Analysis.--Calcd. for C H N N, 11.66. Found: N,f

Hydrochloride salt.-To a solution of 24.0 g. of N,-N'-" disubstituted hydrazine base (0.1 mole) in 240 cc. or: anhyd. ethyl ether was added, with cooling, ethereal HCll. After chilling, the solid is filtered ofi and re; crystallized from hot isopropyl alcohol, M.P. 152-153? to pH 1.

0. Yield 24.7 g. (89.2%).

Analysis.Calcd. for C H N Cl: N, 10.12; Cl, 12.81. Found: N, 10.27; Cl, 12.75.

EXAMPLE 38 3-phenylpr pylhydrazine and hydrochloride salt To 88.5 g. (1.5 moles) of hydrazine hydrate in 450 cc. of ethanol was added at reflux temperature g. (0.50 mole) of 3-phenylpropylbromide in cc. of ethanol. The mixture was refluxed with stirring for 2 hours. The mixture was concentrated on the water bath by vacuum distillation. The residue was made strongly alkaline with potassium hydroxide solution and the alkaline solution extracted with ether. The ether extracts were dried with potassium carbonate and the product collected by distillation in vacuo, B.P. 8895 C. (0.50 mm.), yield 38 g. (50%).

Hydrochloride salt-The hydrochloride salt was prepared in isopropyl alcohol by the addition of ethereal hydrochloric acid, yield 24 g., M.P. 137139 C.

Analysis.--Calcd. for cgH15ClN2: Cl, 19.03; N, 15.01. Found: Cl, 19.30; N, 15.16.

For the preparation of the intermediate ketones (1- aryl-2-propanones) the method of H. B. Haas, A. Susie and R. Heider (J. Org. Chem, 15, 8 (1950)) was followed. Ketones not mentioned in the literature which were prepared are:

1-(3,4'-methylenedioxy)-phenyl-2-propanone, B.P. 80 C. (0.08 mm), N 1.5420.

Analysis.-Calcd. for C H O CO, 1574. Found: CO, 1519.

1-(3,4,5-trimethoxy)-phenyl-2-propanone, B.P. C. (0.03 mm), M.P. 67-68 0., N 1.5319.

Analysis.Calcd. for C H O CO, 12.49. Found: CO, 12.27.

1-(3'-chloro)-phenyl-2-propanone, B.P. 75 C. (0.06 mm.), N 1.5350.

Analysis.Calcd. for C H ClOz Cl, 21.03. Found: Cl, 20.73.

Various changes and modifications of the invention can be inade and, to the extent that such variations incorporate the spirit of this invention, they are intended to be included within the scope of the appended claims.

What is claimed is:

1. N-(3-phenyl-2-propyl)hydrazine. 5

2. 3,4-methylenedioxyphenyl isopropylhydranine.

3. l-hydrazino-Z-phenylpropane.

4. :N-[S -(p-:nethoxyphenyl) -2-propyl] hydrazine.

5. N-(4-phenyl-2-buty1)hydrazine.

6. N-[3-(o-methylphenyl) -2-propyl] hydrazine.

7. N-(l-phenyl-Z-propyl)-N'-isopropy1 hydrazine.

8. 1-(3',4-dimethoxypheny1)-2-propyl hydrazine.

9. Compounds of the group consisting of compounds of the formulae and nontoxic acid addition salts thereof, wherein R is a member of the group consisting of hydrogen and at least 25 one of the group consisting of lower alkyl, lower alkoxy, phenyl, phenyl-lower alkyl, phenylmethoxy, phenoxy, hydroxy, lower alkylenedioxy, bromine and chlorine, R is a inem ber of the group consisting of hydrogen, low alkyl, cyclohexyl, cyclopentyl, phenethyl, phenylpropyl and 30 phenylisopropyl, R is a member of the group consisting of hydrogen, lower alkyl, lower alkenyl, phenyl, 'hydroxyphenyl, methoxyphenyl, chlorophenyl, acetoxyphenyl, phenethyl, phenylpropyl, phenylisopropyl, cyclopentyl and cyclohexyl, Y is a bran'ohed alkylene group having lid at least two oaihons thereof in a line between the phenyl and hydrazine groups and said alkylene group having not more than a total of 5 carbons in the whole chain, Z is alkylene, R is a member of the group con --en+-en-Nn-=nn.

Jan. "15. The compound QoE-oiL-NE-NH.

on. on:

References Cited in the file of this patent UNITED STATES PATENTS Schumann Apr. 19 1960 Schumann Apr. 19,, 1960 OTHER REFERENCES Votooek Tet a1.: Cheniioal Abstracts, vol. 26, p. 5294 1932 Yaleet LAm. Chem. see, vol. '75, p 1933 1953).

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No, 3,000,903 I, September; 19} 1961 John H, B161 It is hereby certified that error appears in the above numberedpatent requiring correction and that the said Letters Patent should read'as corrected below. a

Columns 3 and 4, Tablel, in the heading to the second column, for read' column 5, line 64, for "R,", second occurrence, read R column 7, line 47, for "be" read by line 51, for "N-nitroso-N-lower alkyl or aralkyl-N-(phen" read hydrazine. This reaction may be represented column 8, lines 58 and 59, strike out "Powders l,- 2 and 3 are slugged, then granulated, mixed with 4 and 5, and tableted column 9, line 72, after "yield" insert 100 g. column. 10, line 9,, strike out "'lbs."; column 12, line 56, for "709" read 7,0 column 13, line 38, for "1706" read 17,06 line 89, ior "1636" read 16,36 column 14, line 9, for "1960"" d 86 column 18,- line-65, for "1574" read 1574 line 66, for "1519" read 15. 19

Signed and sealedthis 6th day of February 1962.

(SEAL) Attest:

ERNEST W. SWIDER DAVID L. LADD' Attesting Officer Commissioner of Patents 

2. 3,4-METHYLENEDIOXYPHENYL ISOPROPYLHYDRAZINE.
 9. COMPOUNDS OF THE GROUP CONSISTING OF COMPOUNDS OF THE FORMULAE 